Lymphoma in the Tofacitinib Rheumatoid Arthritis Clinical Development Program

OBJECTIVE: Tofacitinib is an oral JAK inhibitor indicated for the treatment of rheumatoid arthritis (RA). We characterized lymphoma events in the tofacitinib RA clinical development program. METHODS: Lymphoma events (up to March 2015) were identified from 19 tofacitinib studies (2 phase I, 9 phase II, 6 phase III, and 2 long‐term extension) of patients with moderate to severe RA. Patients in these studies received tofacitinib dosed at 1–30 mg twice daily or 20 mg once daily, as monotherapy or with conventional synthetic disease‐modifying antirheumatic drugs. Lymphoma incidence rates (IRs; number of patients with events/100 patient‐years) and standardized incidence ratios (SIRs) were calculated. A descriptive case–matched control analysis (1:4) was performed to identify potential risk factors for lymphoma. RESULTS: A total of 6,194 patients received tofacitinib (19,406 patient‐years of exposure, 3.4 years median treatment duration). Nineteen lymphomas occurred (IR 0.10 [95% confidence interval (95% CI) 0.06–0.15]), with no increase observed with time of exposure. The age‐ and sex‐adjusted SIR of lymphoma was 2.62 (95% CI 1.58–4.09) (Surveillance, Epidemiology, and End Results [SEER] program database). The clinical characteristics of the 19 lymphomas were typical for the RA population. Three lymphomas were positive for Epstein‐Barr virus, 8 were negative, 2 were equivocal, and 6 were untested. Numerically, more lymphoma cases had a history of Sjögren's syndrome and were positive for anti–cyclic citrullinated protein and rheumatoid factor at baseline versus matched controls. The mean corticosteroid dose was higher for lymphoma cases versus controls. CONCLUSION: In the tofacitinib RA clinical development program, lymphoma rates were stable over time and there were minimal differences in the baseline characteristics of patients with and without lymphoma.